Glaucoma is a progressive optic neuropathy caused by a pathological loss of the retinal neurons that form the optic nerve from the eye to the brain. t is a leading cause of irreversible blindness in the United States; approximately 2.2 million people older than 40 years of age suffer from the disease and as many as 120,000 of these people are blind from glaucoma. As the population ages, the disease will become an increasingly important problem of public health, but treatments are effective in preventing or slowing vision loss and it is, therefore, important to optimize procedures for determining if treatment is needed and if it is effective. Because the cause of glaucoma is unknown, the diagnosis or progression of disease requires ophthalmic testing to identify and quantify clinical characteristics of glaucomatous neuropathy, such as the pattern of visual field defects, anatomical changes of the optic nerve head, and losses of retinal ganglion cells and axons. The goal of the proposed research is to gain a better understanding of the relationships between clinical measures of neural and visual losses from glaucoma, especially the psycho-physiological links between structure and function. The principal experiments involve behavioral studies of visual function (standard automated perimetry) and high resolution imaging of retinal structure (optical coherence tomography) over the time course of experimental glaucoma in macaque monkeys. The data from the investigations of experimental glaucoma will be used to 1) develop a quantitative model relating the loss of retinal neurons in a specific area of the retia to the number of axons entering the optic nerve from the same retinal area and 2) To investigate the temporal relationships of the clinical signs of glaucomatous neuropathy that involve losses in visual sensitivity, increased cupping of the optic nerve head, and thinning of the neuronal layers of the inner retina. In the final phase, the relationships that were derived from experimental glaucoma in monkeys will be applied to assess the severity, or stage, of glaucoma in human patients. The research method is based on defining procedures with experimental glaucoma where there are excellent controls for the experimental and measurement variables and, then, application to human patients to test the clinical relevance and validity of the procedures. This method of going from the laboratory to the clinic should maximize the potential for significant new information about ophthalmic testing for translation to the diagnosis and assessment of glaucoma. Key words: glaucoma, retinal ganglion cells, retinal nerve fiber layer, perimetry, OCT, optic nerve head, monkeys, humans PUBLIC HEALTH RELEVANCE: Glaucoma is a significant public health problem affecting 2.2 million individuals in the United States, of which 120,000 are legally blind. The treatment and management of the disease is estimated to have a direct financial burden of $2.9 billion, with the care of more advanced cases costing up to four times those of early stages. Treatment is effective in preventing or slowing vision loss and it is, therefore, important to optimize procedures for determining when treatment is needed and when it is effective. The goal of this project is to improve the accuracy and precision of in clinical measures of the stage of optic neuropathy to aid in the early diagnosis and management of this sight threatening disease.